ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3775G>A (p.Ala1259Thr) (rs776478974)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000251253 SCV000319443 uncertain significance Cardiovascular phenotype 2015-02-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV000321117 SCV000425543 likely benign Ehlers-Danlos syndrome, type 4 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000321117 SCV000756047 uncertain significance Ehlers-Danlos syndrome, type 4 2017-09-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1259 of the COL3A1 protein (p.Ala1259Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs776478974, ExAC 0.1%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual and in an independent family affected with a COL3A1-related disease (PMID: 25758994, 28035354). ClinVar contains an entry for this variant (Variation ID: 263915). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.